He was inspired by Louis Agassiz to pursue his studies in ichthyology. He taught natural history courses at several small Midwestern colleges before joining the natural history faculty of Indiana University Bloomington in 1879. In 1885, he was named President of Indiana University, becoming the nation's youngest university president at age 34 and the first Indiana University president that was not an ordained minister.[4] He improved the university's finances and public image, doubled its enrollment, and instituted an elective system which, like Cornell's, was an early application of the modern liberal arts curriculum.[3]

In March 1891, he was approached by Leland and Jane Stanford, who offered him the presidency of their about-to-open California university, Leland Stanford Junior University. He had been recommended to the Stanfords by the president of Cornell, Andrew White. His educational philosophy was a good fit with the Stanfords' vision of a non-sectarian, co-educational school with a liberal arts curriculum, and after consulting his wife he accepted the offer on the spot.[3] Jordan arrived at Stanford in June 1891 and immediately set about recruiting faculty for the university's planned September opening. With such a short time frame he drew heavily on his own acquaintance in academia; of the fifteen founding professors, most came either from Indiana University or his alma mater Cornell. During his first year at Stanford he was instrumental in establishing the university's Hopkins Marine Station. He served Stanford as president until 1913 and then chancellor until his retirement in 1916.[4] While chancellor, he was also elected president of the National Education Association.[6]

In addition to his work as Stanford president, Jordan was known for being a peace activist. He argued that war was detrimental to the human species because it removed the strongest organisms from the gene pool. Jordan was president of the World Peace Foundation from 1910 to 1914 and president of the World Peace Conference in 1915, and opposed U.S. involvement in World War I.[4]

In 1905, Jordan launched an apparent coverup of the murder by poisoning of Jane Stanford. While vacationing in Oahu, Stanford had suddenly died of strychnine poisoning, according to the local coroner’s jury. Jordan then sailed to Hawaii, hired a physician to investigate the case, and declared she had in fact died of heart failure, a condition whose symptoms bear no relationship to those actually observed.[10][11] His motive for doing this has been a subject of speculation. One possibility is that he was simply acting to protect the reputation of the university;[10][12] its finances were precarious and a scandal might have damaged fundraising. He had written the president of Stanford's board of trustees offering several alternate explanations for Mrs. Stanford's death, suggesting they select whichever would be most suitable.[10] Given that Mrs. Stanford had a difficult relationship with him and reportedly planned to remove him from his position at the university, he might have had a personal motive to eliminate suspicions that might have swirled around an unsolved crime.[13] Jordan's version of Mrs. Stanford's demise[14] was largely accepted until the appearance of several publications in 2003 emphasizing the evidence that she was murdered.[10][12][13][15]

His son, Eric Knight Jordan (1903–1926)[16] followed his father's footsteps into the sciences. He had taken part in a successful paleontological expedition to the Revillagigedo Islands and was considered a rising star in the world of paleontology when he was involved in a traffic accident near Gilroy, California, suffering fatal injuries and dying at the age of 22.[17] His death was a severe blow to his father.[18]

The David Starr Jordan Prize was established in 1986 as a joint endowment by Cornell, Indiana University, and Stanford. It is awarded to a "young scientist (40 years of age or less) who is making novel innovative contributions in one or more areas of Jordan’s interest: evolution, ecology, population and organismal biology".[20]

David Starr Jordan "Namesake Tree" at the University of Hawai‘i at Mānoa Campus Arboretum, an Indian Rubber Tree (Ficus elastica) given to Jordan at the outset of a trip to Japan, and planted by him on December 11, 1922,[23] now listed as an Exceptional Tree of Hawai‘i.[24]